Hypersensitivity is defined as a state of altered reactivity in which the body reacts with an exaggerated immune response to a substance (antigen). Hypersensitivity may be caused by exogenous or endogenous antigens. Hypersensitivity reactions underlie a large number of diseases. Among these, allergic and autoimmune conditions are of great importance. A classification of hypersensitivity diseases is given in the textbook Clinical Medicine (Kumar, P. and Clark, M.: “Clinical Medicine”, 3rd edition, p. 147-150, 1994, Bailliere Tindall, London).
Type I hypersensitivity reactions (IgE mediated allergic reactions) are caused by allergens (specific exogenous antigens), e.g. pollen, house dust, animal dandruff, moulds, etc. Allergic diseases in which type I reactions play a significant role include asthma, eczema (atopic dermatitis), urticaria, allergic rhinitis and anaphylaxis.
Type II hypersensitivity reactions are caused by cell surface or tissue bound antibodies (IgG and IgM) and play a significant role in the pathogenesis of myasthenia gravis, Good-pasture's syndrome and Addisonian pernicious anaemia.
Type III hypersensitivity reactions (immune complex) are caused by autoantigens or exogenous antigens, such as certain bacteria, fungi and parasites. Diseases in which type III hypersensitivity reactions play a significant role include lupus erythematosus, rheumatoid arthritis and glomerulonephritis.
Type IV hypersensitivity reactions (delayed) are caused by cell or tissue bound antigens. This type of hypersensitivity plays a significant role in a number of conditions, e.g. graft-versus-host disease, leprosy, contact dermatitis and reactions due to insect bites.
Type I to type IV hypersensitivity reactions are all classically allergic reactions, which may lead to histamine release. However, hypersensitivity reactions are also those, where histamine release is triggered through the directly action of “triggering substances” with the cellular membrane. Examples of “triggering substances” are, but not limited to, toxins, food constituents and certain drugs.
A number of drug classes are available for the treatment of hypersensitivity and related inflammatory reactions.
Among these, the corticosteroids are some of the most widely used drugs. Corticosteroids primarily exert their pharmacological action by non-selectively inhibiting the function and proliferation of different classes of immune cells resulting in suppression of hypersensitivity reactions. Unfortunately, the corticosteroids are associated with a number of serious side effects, e.g. immunosuppression, osteoporosis and skin atrophy. Alternative drugs are associated with serious toxicity. There is a strong need for effective and safer alternatives to the existing antiinflammatory drugs.
Often hypersensitivity or inflammatory disease as described above is associated with or even caused by pathogenic bacteria, fungi or viruses. A number of pathogenic bacteria and fungi play an essential role in the development of a plethora of diseases, including skin diseases. For example, atopic dermatitis, which is widely considered as an inflammatory skin disorder is often associated with secondary infections, e.g. with Staphylococcus Aureus, thus giving rise to aggravation of the symptoms. Similarly, the facial eczematous disease seborrheic dermatitis is associated with fungal infections, typically caused by Pityrosporum ovale. Today, such skin diseases are often treated with corticosteroids. Antibiotics may also be applied, but today the topical application of traditional antibiotics is limited due to the risk of adverse effects and development of resistant strains of micro organisms, which can cause severe problems.
Herpes labialis (cold sores) is associated primarily with unpleasant inflammation and blisters occurring on the lips and face as the primary symptoms, but the cause of the disease is a viral infection with Herpes simplex type 1.
Similarly, acne vulgaris is an inflammatory disease of the sebaceous glands and hair follicles of the skin, but a primary cause of the disease is a bacterial infection with Propionibacterium acnes. 
Infections are treated with antibiotics with diverse specific mechanisms of action and often associated with unpleasant adverse effects. Unfortunately antibiotics often give rise to the development of resistance. Resistant strains of bacteria, which are practically untreatable, are a growing problem due to the widespread use of antibiotics.
Obviously there is a strong need for safer antibiotics and treatments that combine antibacterial, antiviral or antifungal effects with symptom relieving antiinflammatory effects.
Niacinamide, which is also known as nicotinamide, has been found to be a potent inhibitor of poly(ADP-ribose)polymerase.
Poly(ADP-ribose)polymerase, also known as poly(ADP-ribose)synthetase or poly(ADP-ribose)transferase is an nuclear enzyme that catalyses the posttranslational modification of nuclear proteins by covalent attachment of ADP-ribosyl moieties derived from NAD+ with an accompanying release of nicotinic acid amide. Preferred acceptor proteins are nuclear histones, whose poly-ADP-ribosylation induces local alterations in the architecture of chromatin domains.
Inhibitors of poly(ADP-ribose)polymerase have been found to suppress hypersensitivity reactions and inflammation. Thus, Ungerstedt et al. (Clin Exp Immunol. 2003 January; 131(1):48-52) found that niacinamide inhibits the expression in human whole blood of the pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α. This may explain some of the beneficial effects reported, e.g. in the prophylaxis of aggravation of diabetes and symptoms of osteoarthritis as elaborated by McCarthy et al (Med Hypotheses. 1999 October; 53(4):350-60). Still niacinamide and similar pyridine carboxy derivatives are considered as mild and speculative antiinflammatory agents, which is also why they are not at present in established clinical use.
JP 964497 discloses the use of niacinamide for preventing mildew and for use as a food preservative. There is no mention of medicinal use or use as an antibiotic.
Disinfecting properties of fatty acids have been acknowledged for more than a century. The use of bar soap is a practical example of this, which besides solubilization of dirt also provides a mild degree of disinfection of the skin. The acknowledgement of the preferable use of certain fatty acids or derivatives thereof for inhibition of microorganisms is exemplified by U.S. Pat. No. 4,002,775, which discloses the use of specific fatty acids and derivatives as antimicrobial agents in relation to food preservation.
EP 465423 discloses a pharmaceutical composition for killing microorganisms containing fatty acids and monoglycerides thereof. Fatty acid esters of other glycols are not disclosed and the combination or complex formation with pyridine carboxy derivatives is not mentioned. Therefore the relevance to the present invention is limited.
The same is the case with WO 9820872, which discloses a method for counteracting infection of the genital mucosa of a mammal by applying compositions containing C6 to C18 fatty acids or monoglycerides or fatty alcohol esters thereof to the genital mucosa.
U.S. Pat. No. 5,231,087 discloses a method of treating certain skin diseases and tumours with esters and amides of monocarboxylic acids having 9 to 18 carbon atoms. The proposed esters include esters of a broad variety of alcohols ranging from monohydric alcohols up to esters of saccharides and polyethylene glycol, which is completely besides the scope of the present invention. Furthermore there is no disclosure of combination or complex formation with pyridine carboxy derivatives.
As recognised by the present inventor, there is a need for agents that provide combined anti-inflammatory and anti-microbial therapeutic effects in an efficient manner and without the adverse effects associated with existing medication.